1. Technical Field
The present invention relates to bio-erodible ophthalmic shields and methods for their use, for example as a protective shield following eye surgery or other trauma to the eye. More specifically, the invention provides improved, gelatin-based bio-erodible ophthalmic shields that provide improved physical and therapeutic properties under a variety of physiological conditions of a traumatized or non-traumatized human eye.
2. Brief Description of the Background Art
The preparation of collagen-based ophthalmic shields ("collagen shields") and their use both with and without the incorporation of therapeutic agents (i.e., drugs for ocular administration) have been described in the literature. See, for example, Kaufman, "Collagen shield drug delivery: Therapeutic concentrations of tobramycin in the rabbit cornea and aqueous humor," J. Cataract Refract. Surg., 14:500-504 (1988). Collagen of porcine or bovine origin often is employed, but, no matter what its source, the collagen first typically is solubilized by enzymatic treatment. The in vivo solubility or "bio-erodibility" of corneal shields prepared from enzyme-solubilized collagen is controlled by controlling the extent to which the collagen is cross-linked, either chemically or via the use of ultraviolet light. Inasmuch as native collagen is not soluble under normal physiologic conditions, control over the solubilization and cross-linking processes can be critical to the preparation of a final product having the desired dissolution rate. Unfortunately, variations in processing, raw material sources and other factors can make the wide-scale commercial production of such final products difficult.
Ophthalmic shields find one potential utility in the treatment of the traumatized (physically injured or post-surgery) eye by acting as a temporary protective bandage. Trauma, which may be caused for example by accidental injury or eye surgery, may be treated in part by the application of a corneal shield which serves to protect the tissue from irritation and infection, and fosters the growth of epithelial cells, thus providing increased patient comfort. Ideally, the ophthalmic shield could be comfortably worn for a period of several days while providing lubrication for the eye, physical protection from irritation and a favorable environment which fosters the healing process. Aquavella et al., "Therapeutic Applications of a Collagen Bandage Lens: A Preliminary Report," The CLAO Journal, 14:1 (1988) discusses the use of a "collagen bandage lens" following anterior segment surgery.
Not only can ophthalmic shields be used to protect the traumatized eye, but they also may be used to promote healing of the traumatized eye, thus decreasing the time required for healing. Poland et al., "Clinical Uses of Collagen Shields," J Cataract Refract Surg, 14:489-491 (1988) discusses clinical uses of collagen shields, including increased patient comfort, enhancement of epithelial healing, and drug delivery following surgery such as keratoplasty.
Ophthalmic shields also have been proposed for use as ocular drug delivery devices. The literature (Aquavella et al., "Use of Collagen Shields as a Surgical Adjunct," J. Cataract Refract. Surg., 14:492-95 (1988)) contains reports of pilocarpine, tobramycin, gentamicin, dexamethasone and flurbiprofen being administered to the eye of a patient after being incorporated into a collagen-based ophthalmic shield. Collagen-based ophthalmic shields also can provide for the sustained delivery of a pharmaceutically active agent. The shield can be placed in the eye, such as in the inferior fornix or the inferior cul-de-sac, where it slowly dissolves under physiological conditions and slowly releases the drug.
Ophthalmic shields may also be used in the treatment of dry eye syndrome. The traditionally used artificial tear solutions have limited effectiveness because of their short retention time within the conjunctival sac. When long-acting, soluble, tear replacement preparations have been administered, ocular irritation and blurring of vision often resulted. In contrast, the literature reports that a collagen film inserted into the inferior cul-de-sac of normal patients dissolved over approximately seven hours and produced a prolonged tear film break-up time, without irritation or blurring. (Shaker et al., "Soluble Collagen Disks for the Treatment of Dry Eye Syndrome," The CLAO Journal, 15:4 (1989)). The collagen shields dissolve in the eye, becoming gel-like and eventually liquefying, thereby providing the "dry eye" with lubrication.
Excimer laser keratectomy has been widely described in the scientific literature and shows much promise for achieving commercial success as a surgical procedure for vision correction (e.g. correction of myopia) for human patients. Successful treatment of the eye that has been traumatized by the excimer laser keratectomy procedure, and successful wound healing in the eye, are important aspect of the total surgical care of the patient. This aspect of patient care is expected to be an important aspect of commercial success enjoyed by that surgical procedure.
The literature describes the use of collagen-based ophthalmic shields for, for example, ocular drug delivery and wound healing applications. See Shofner et al., "New Horizons in Ocular Drug Delivery," Ophthalmology Clinics of North America, 2:15-23 (1989); Aquavella et al., "Therapeutic Applications of a Collagen Bandage Lens: A Preliminary Report," The CLAO Journal, 14:1 (1988); Marmer, R., "Therapeutic and protective Properties of the Corneal Collagen Shield," J Cataract Refract Surg., 14:496-499 (1988); Poland et al., "Clinical Uses of Collagen Shields," J Cataract Refract Surg, 14:489-491 (1988). However, due to the triple helix structure of collagen, collagen often exhibits unacceptable dissolution properties. Moreover, collagen ophthalmic shields can suffer from poor optical clarity. Therefore, a need exists for an ophthalmic shield with the properties of improved optical clarity and improved dissolution in traumatized, non-traumatized and "dry" eyes.
Additionally, the improved ophthalmic shield must exhibit good physical properties, especially optical clarity and bio-erodibility, in the environments of traumatized, non-traumatized and dry eyes. The physical, chemical and enzymatic characteristics of the normal eye differ from that of the traumatized eye following, for example, accidental injury or surgery. Normal human eyes exhibit a relatively constant tear rate, having a chemical and enzymatic composition that has been described in the literature. Lysozyme, an enzyme that hydrolyses the muramic acid linkages in the peptidoglycan of bacterial cell walls, is prevalent in the tears of the normal human eye. This enzyme plays an important bacteriocidal role in the tears. In the traumatized eye, however, tearing often is greatly increased, thereby diluting the normal complement of lysozyme and rendering the already-compromised eye susceptible to bacterial infections. The traumatized eye also exhibits elevated levels of a number of proteolytic enzymes, such as the collagenases. It has been found, for example, that enzyme levels can be very high following excimer laser eye surgery (photorefractive keratectomy). The condition known as dry eye, in contrast, is characterized by the presence of elevated levels of plasminogen. Collagen shields currently available tend to behave differently in the chemically--and enzymatically-different environments of the dry eye, the non-traumatized eye and the traumatized eye. Thus, a need has existed for an improved ophthalmic shield that would exhibit good physical properties, especially optical clarity, comfort and bio-erodibility characteristics, in these various conditions in the human eye.